Department of Pharmacognosy, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688 Kraków, Poland.
Toxicol In Vitro. 2021 Oct;76:105231. doi: 10.1016/j.tiv.2021.105231. Epub 2021 Aug 4.
The anti-melanoma potential of galactolipids: MGDG-1 and DGDG-1, isolated from Impatiens parviflora, and their synergistic effect with anticancer drug - doxorubicin (DOX) was investigated. Both compounds demonstrated time- and dose-dependent cytotoxicity against human melanoma cells of different metastatic potential. MGDG-1 was more effective than DGDG-1, with the highest activity against A375 cell line (IC = 15.14 μg/mL). Both compounds acted selectively, were devoid of hepatotoxicity or mutagenicity. Additionally, MGDG-1 proved to be a tyrosinase inhibitor. Co-administration of MGDG-1 and DGDG-1 with DOX revealed a synergistic cytotoxic effect on melanoma cells. The cytotoxicity of all tested MGDG-1/DOX and DGDG-1/DOX cocktails was considerably higher than that of each agent administered alone. MGDG-1/DOX (Mix3) reduced the viability of A375 melanoma cells almost totally and this effect was 2-fold more potent as compared to DOX alone. Our study indicates that the overall effect is enhanced with the increasing concentration of MGDG-1 in the cocktail. These results open up a possibility for lowering therapeutic doses of chemotherapeutics such as doxorubicin when co-administrated with galactolipids. Thus, MGDG-1 can be prospectively considered as multidirectional anti-melanoma agent and can be recommended for further in vitro and in vivo studies, especially in search for effective combined therapy.
菜蓟宾二葡萄糖基甘油二酯和二葡萄糖基甘油二酯对人黑色素瘤细胞的协同抗肿瘤作用及其机制研究。从非洲凤仙花中分离得到的半乳糖脂 MGDG-1 和 DGDG-1 对不同转移潜能的人黑色素瘤细胞具有时间和剂量依赖性细胞毒性。MGDG-1 比 DGDG-1 更有效,对 A375 细胞系的活性最高(IC=15.14μg/mL)。两种化合物均具有选择性,无肝毒性或致突变性。此外,MGDG-1 被证明是一种酪氨酸酶抑制剂。MGDG-1 和 DGDG-1 与 DOX 联合使用对黑色素瘤细胞表现出协同的细胞毒性作用。所有测试的 MGDG-1/DOX 和 DGDG-1/DOX 鸡尾酒的细胞毒性均明显高于单独使用每种药物的细胞毒性。MGDG-1/DOX(Mix3)使 A375 黑色素瘤细胞的活力几乎完全降低,其效果比单独使用 DOX 强 2 倍。我们的研究表明,随着鸡尾酒中 MGDG-1 浓度的增加,整体效果增强。这些结果为降低化疗药物(如阿霉素)的治疗剂量提供了可能性,当与半乳糖脂联合使用时。因此,MGDG-1 可以作为一种多方位的抗黑色素瘤药物,并且可以推荐用于进一步的体外和体内研究,特别是在寻找有效的联合治疗方法时。